The term acne comes from a corruption of the Greek {acute over (α)}κμ{acute over (η)} (acme in the sense of a skin eruption). The most common form of acne is known as “acne vulgaris”, meaning “common acne”. Many teenagers get this type of acne.
Acne vulgaris is a skin disease; caused by changes in the pilosebaceous units (skin structures consisting of a hair follicle and its associated sebaceous gland). Severe acne is inflammatory, but acne can also manifest in non-inflammatory forms. Acne lesions are commonly referred to as pimples, spots, or zits.
Acne is most common during adolescence, affecting more than 85% of teenagers, and frequently continues into adulthood. For most people, acne diminishes over time and tends to disappear, or at least decrease, after one reaches his or her early twenties. There is, however, no way to predict how long it will take for it to disappear entirely, and some individuals will continue to suffer from acne decades later, into their thirties and forties and even beyond.
Acne develops as a result of blockages in follicles. Formation of a plug of keratin and sebum (a microcomedo) is the earliest change. Enlargement of sebaceous glands and an increase in sebum production occur with increased androgen (DHEA-S) production. The microcomedo may enlarge to form an open comedo (blackhead) or closed comedo (whitehead). In these conditions the naturally occurring largely commensual bacteria Propionibacterium acnes can cause inflammation, leading to inflammatory lesions (papules, infected pustules, or nodules) in the dermis around the microcomedo or comedo, which results in redness and may result in scarring or hyperpigmentation.
Rosacea is a common but often misunderstood condition that is estimated to affect over 45 million people worldwide. It affects white-skinned people of mostly north-western European descent, and has been nicknamed the ‘curse of the Celts’ by some in the British Isles. It begins as erythema (flushing and redness) on the central face and across the cheeks, nose, or forehead but can also less commonly affect the neck and chest. As rosacea progresses, other symptoms can develop such as semi-permanent erythema, telangiectasia (dilation of superficial blood vessels on the face), red domed papules (small bumps) and pustules, red gritty eyes, burning and stinging sensations, and in some advanced cases, a red lobulated nose (rhinophyma). The disorder can be confused and co-exist with acne vulgaris.
Patients with rosacea suffer from redness, stinging, burning and chronic inflammation that results in sensitive skin and intolerance of many topical products. Drugs for treatment of rosacea must ideally be both clinically efficacious and coexist in a vehicle designed for sensitive skin. Most vehicles, such as propylene glycol and fatty acids damage the stratum corneum in order to allow a topical drug to penetrate adequately.
There are a variety of compositions available for treating inflammatory acne vulgaris and rosacea, including topical and systemic antibiotics and retinoids. Azelaic acid, or nonanedioic acid, has been used to effectively treat acne. However, at higher concentrations, particularly at prescription strength, azelaic acid may be irritating to skin. At lower concentrations, effectiveness of the acid is compromised. Carriers such as alcohols added to enhance absorption of the acid at lower concentrations may cause drying of the skin and hence additional irritation. It would be desirable to provide an effective treatment composition for acne vulgaris and rosacea that is non-irritating and non-drying yet allow for effective release of azelaic acid from the vehicle and subsequent rapid penetration into the skin.
Ideal topical drugs for rosacea should not damage the skin barrier function and enhance hydration while allowing such difficult-to-dissolve drugs as azelaic acid to be solubilized and bioavailable.
In an attempt to increase penetration of azelaic acid into skin, formulations containing hydrogels consisting of triglyceride, propylene glycol, at least one polysorbate, polyacrylic acid and soy lecithin have been devised. These vehicles deliver more azelaic acid into the skin than the prior art. Despite greater penetration into the skin, formulations with 15% azelaic acid (Finacea™) utilizing this patented vehicle have been found to be significantly more irritating when compared to other rosacea topical treatments such as metronidazole 0.75%.
Patient compliance is very important to the success of medical treatment. In diseases such as rosacea, acne, and seborrheic dermatitis, there exists heightened skin sensitivity. In a study by the manufacturer of azelaic acid 15% gel (Finacea™) for rosacea; over 30% of treated patients complained of burning, stinging or tingling. This side effect would be expected to significantly and negatively impact patient compliance. Ideally, a vehicle should not only effectively deliver azelaic acid to the skin but should do so rapidly in order to minimize irritation and hypersensitivity.
There is a need for delivery of effective concentrations of azelaic acid to the skin while minimizing irritation. The present invention allows for enhanced delivery of azelaic acid while minimizing irritation, thus encouraging optimal patient compliance.